The research intends to extend our ability to perform single cell mutation detection of genetic diseases to the molecular detection of aneuploidy in single cells in a way that can be applied to the study of meiotic errors and eventually preimplantation genetic diagnosis. We propose to study DNA polymorphisms within single polar bodies and oocytes as an alternative means for assessing the validity of problematic cytogenetic observations of meiosis I errors. Nonfertilizing oocytes obtained after IVF and polar bodies biopsied from each will be subjected to single cell whole genome amplification using primer extension preamplification (PEP). Oocytes and polar bodies will be analyzed for segregation of chromosomes to test if there is reduced recombination with advanced maternal age, and whether this accounts for the high rate of non-disjunction in older women. These technologies will provide genetic information for each oocyte-polar body pair that is otherwise unobtainable using conventional cytogenetics or fluorescent in situ hybridization (FISH). These data should test directly several model of meiosis I non-disjunction. A detailed investigation into these fundamental reproductive processes may elucidate the mechanisms behind the high frequency of aneuploidy in human gametes, miscarried conceptuses, and liveborn children.